Placental tissue grafts modified with a cross-linking agent and methods of making and using the same

Abstract

Described herein are tissue grafts derived from the placenta that possess good adhesion to biological tissues and are useful in would healing applications. In one aspect, the tissue graft includes (1) two or more layers of amnion, wherein at least one layer of amnion is cross-linked, (2) two or more layers of chorion, wherein at least one layer of chorion is cross-linked, or (3) one or more layers of amnion and chorion, wherein at least one layer of amnion and/or chorion is cross-linked. In another aspect, the grafts are composed of amnion and chorion cross-linked with one another. In a further aspect, the grafts have one or more layers sandwiched between the amnion and chorion membranes. The amnion and/or the chorion are treated with a cross-linking agent prior to the formation of the graft. The presence of the cross-linking agent present on the graft also enhances adhesion to the biological tissue of interest. Also described herein are methods for making and using the tissue grafts.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. provisional patent application No. 61 / 683,697, filed on Aug. 15, 2012. The content of the prior application is incorporated herein by reference in its entirety.BACKGROUND[0002]The human spinal cord and brain are covered with the meninges membranes, consisting of three overlapping layers of tissue including the outermost dura mater, arachnoid mater and innermost pia mater. The meningeal membranes are critical to the operation of the central nervous system and their disruption, by accident or surgical intervention, can cause serious consequences unless repaired. Dural tears are common complications in spine surgery and can range in size from nonleaking pinholes to large defects that require tissue reconstruction with a patch. A persistent tear can lead to severe headaches, CSF fistula, formation of a pseudocyst, nerve root entrapment and fluid collection. Large retrospective series have reported an i...

AI Technical Summary

Benefits of technology

[0007]Described herein are tissue grafts derived from the placenta that possess good adhesion to biological tissues and are useful in would healing applications. In one aspect, there is provided a homologous or heterologous tissue graft comprising two or more layers of amnion and / or chorion wherein at least one of the layers is internally cross-linked, at least one of the layers is externally cross-linked with a second layer, or a combination thereof. In another aspect, the tissue graft includes (1) two or more layers of amnion, wherein at least one layer of amnion is cross-linked, (2) two or more layers of chorion, wherein at least one layer of chorion is cross-linked, or (3) one or more layers of amnion and chorion, wherein at least one layer of amnion and / or chorion is cross-linked. In another aspect, the grafts are composed of amnion and chorion cross-linked with one another. In a further aspect, the grafts have one or more layers of non-amnion and / or non-chorion material sandwiched between the amnion and chorion membranes. The amnion and / or the chorion are treated with a cross-linking agent prior to the formation of the graft. The presence of the cross-linking agent present on the graft also enhances adhesion to the biological tissue of interest. In one embodiment, the surface of the graft that is in contact with the biological tissue is lightly cross-linked. Preferably, ‘lightly cross-linked” means that for each reactive functionality on the surface of the graft, there are 10 to 20 complementary reactive groups on the surface of the biological tissue. Also described herein are methods for making and using the tissue grafts.

Problems solved by technology

The meningeal membranes are critical to the operation of the central nervous system and their disruption, by accident or surgical intervention, can cause serious consequences unless repaired.

Dural tears are common complications in spine surgery and can range in size from nonleaking pinholes to large defects that require tissue reconstruction with a patch.

A persistent tear can lead to severe headaches, CSF fistula, formation of a pseudocyst, nerve root entrapment and fluid collection.

Direct suture repair is routinely used to repair dural tears, but leakage through suture holes can occur.

The use of autologous tissues, however, can lead to prolonged operating time, blood loss and separate incisions.

In addition, the quantity of autologous graft may be inadequate in children.

Xenografts and cross-linked animal-derived collagen matrices can be used as dural patches, but carry the risk of disease transmission.

Fibrin glue is prepared from pooled blood and has the potential to transmit disease.

This natural wound healing cascade in most instances results in the formation of soft tissue adhesions, which either tether, compress, or effect surgical accessibility.

Fibrosis is particularly problematic in post-surgical procedures of the spine.

The scar tissue can engulf the dura and nerve roots, which can ultimately result in the reoccurrence of symptoms similar to those experienced prior to surgery.

Thus, subsequent operations to address the problem may have to be performed, which provides additional inconvenience, costs, and risks to the patient.

These materials possess a variety of disadvantages including poor handling characteristics, undesirable resorption profile, limited fixation capabilities, and limited storage options.

Thus, what is needed are grafts that exhibit good adhesion to body tissues and facilitate wound healing yet that do not possess the disadvantages of commercially available options.

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